1. Technical Field
The present invention relates to iontophoretic electrodes, with particular emphasis on electrodes which are used to administer a drug by means of iontophoresis. Although the preferred embodiment is directed to an electrode packaged in dry form which is to be hydrated immediately prior to use, it is also possible to utilize the apparatus of the invention in connection with electrodes provided in a hydrated form.
2. Background Information
Iontophoresis is a method for delivering an ionic form of a drug through the skin in the presence of an electrical potential. It is typically performed by placing an electrode containing an ionic drug solution in contact with the skin at the location where drug is to be transported. A second electrode is placed on the skin near the first electrode, and voltage is applied sufficient to cause current to pass through the skin, thereby completing the electrical circuit between the electrodes. As current flows, the ionic drug molecules migrate through the skin under the influence of the second electrode. One advantage of iontophoresis is that it is a noninvasive means of administering drug, yet avoids many problems which are encountered in oral administration of drugs.
One of the most common uses of iontophoresis is to administer dexamethasone sodium phosphate for the local treatment of local inflammation, tendinitis, bursitis, arthritis, or carpal tunnel syndrome. Iontophoresis is also frequently used to administer lidocaine hydrochloride to serve as a local anesthetic.
In view of the significant clinical benefits of iontophoretic administration of drugs, much attention has been given to the use of iontophoresis as a method for administering other drugs, and it is anticipated that iontophoresis will develop as a method of choice in an increasing number of applications.
One general class of electrode designs involves the use of a conductive element associated with a compartment or pouch into which a drug solution is introduced. One wall of the pouch typically comprises a permeable barrier, which serves to contain the solution, but permits drug ions to pass therethrough. Examples of such electrodes can be seen in U.S. Pat. Nos. 4,250,878; 4,419,092; and 4,477,971.
Pouch-type designs suffer from several problems. For example, the use of a permeable barrier inhibits thorough and complete wetting of the skin lying thereunder, which results in areas of relatively high electrical resistance. The diffusion rate through the permeable membrane also has an undesirable inhibiting effect upon the rate of drug delivery in comparison to an electrode design wherein the drug is directly against the skin.
Another problem with the pouch designs is the need to guard against leakage of the drug solution from the pouch during use. This requires use of a sealed means for introducing drug solution into the pouch, which increases the cost of this type of electrode.
Pouch designs also suffer from a lack of conformability. This exacerbates the problem of uneven wetting of the skin and results in uneven delivery of drug. Lack of conformability also increases the incidence of skin irritation and burns during iontophoresis because it results in an uneven application of electrical current.
A second class of electrode designs involve the use of a conductive element associated with a gel material for containing ionized drug without the use of a pouch. Examples of such bioelectrodes are found in U.S. Pat. Nos. 4,383,529; 4,474,570; and 4,747,819. Typically, these gel-type electrodes incorporate ionized drug into the gel at the time of manufacture. This makes storage and shipping of the electrode more difficult, and shortens the shelf-life of the electrode because it must be used prior to unacceptable degradation of the drug. Attempts to hydrate the gels at the time of use were generally unsuccessful due to the long time required to obtain uniform hydration. Use prior to full and complete hydration leads to uneven current distribution which, as noted above, can result in skin inflammation or burns. As with pouch designs, the use of gel-type electrodes also fails to completely wet the skin lying thereunder resulting in the problems already discussed.
A third class of electrode design is disclosed in copending U.S. application Ser. No. 07/645,028 now abandoned, filed Jan. 23, 1991, entitled "Hydratable Bioelectrode", and U.S. Pat. No. 5,087,242, filed Jul. 21, 1989 and issued Feb. 11, 1992. The text of said copending application and issued patent is hereby incorporated by reference. This third type of electrode design generally utilizes a conductive element associated with a hydratable element. As described in the copending application and the issued patent, the hydratable element is typically formed of a stack of sheets of a dry crosslinked hydrogel, such as crosslinked polyethylene oxide (PEO).
Although a vast improvement over pouch designs and gel-type designs, the crosslinked hydrogel electrode designs still suffer from several significant disadvantages. For example, the dimensions of a hydratable element utilizing a crosslinked hydrogel design are limited because of the requirement for liquid to penetrate from the edges of adjacent sheets to the center thereof before hydration causes blocking; dimensions in excess of about 5 centimeters have been found to result in imperfect hydration, probably due to collapse of the hydrogel sheets upon hydration, thereby blocking further hydration interior of the blockage. Also, in dry form, the stack of sheets of crosslinked hydrogel is relatively stiff and essentially planar. Both of these factors place limitations upon the size, shape, and uses of the electrode.
Also, some manufacturing problems are encountered when preparing the stack of crosslinked hydrogel sheets. For example, the requirement to bind the stack of sheets together adds manufacturing steps and costs. Additionally, since the sides of adjacent sheets must remain open to entry of liquid at the time of hydration, limitations are placed upon the manner in which the hydratable element may be affixed to the conductive element.